Faculty Collaboration Database

G-protein βγ subunit dimers modulate kidney repair after ischemia-reperfusion injury in rats. Mol Pharmacol 2014 Oct;86(4):369-77

Date

07/17/2014

Pubmed ID

25028481

Pubmed Central ID

PMC4164983

DOI

10.1124/mol.114.092346

Scopus ID

2-s2.0-84907912300 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

Heterotrimeric G-proteins play a crucial role in the control of renal epithelial cell function during homeostasis and in response to injury. In this report, G-protein βγ subunit (Gβγ) dimer activity was evaluated during the process of tubular repair after renal ischemia-reperfusion injury (IRI) in male Sprague Dawley rats. Rats were treated with a small molecule inhibitor of Gβγ activity, gallein (30 or 100 mg/kg), 1 hour after reperfusion and every 24 hours for 3 additional days. After IRI, renal dysfunction was prolonged after the high-dose gallein treatment in comparison with vehicle treatment during the 7-day recovery period. Renal tubular repair in the outer medulla 7 days after IRI was significantly (P < 0.001) attenuated after treatment with high-dose gallein (100 mg/kg) in comparison with low-dose gallein (30 mg/kg), or the vehicle and fluorescein control groups. Gallein treatment significantly reduced (P < 0.05) the number of proliferating cell nuclear antigen-positive tubular epithelial cells at 24 hours after the ischemia-reperfusion phase in vivo. In vitro application of gallein on normal rat kidney (NRK-52E) proximal tubule cells significantly reduced (P < 0.05) S-phase cell cycle entry compared with vehicle-treated cells as determined by 5'-bromo-2'-deoxyuridine incorporation. Taken together, these data suggest that Gβγ signaling contributes to the maintenance and repair of renal tubular epithelium and may be a novel therapeutic target for the development of drugs to treat acute kidney injury.

Author List

White SM, North LM, Haines E, Goldberg M, Sullivan LM, Pressly JD, Weber DS, Park F, Regner KR

Authors

Lauren North MD Assistant Professor in the Otolaryngology department at Medical College of Wisconsin
Kevin R. Regner MD Interim Chair, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cardio-Renal Syndrome
Cell Line
Cell Movement
Cell Proliferation
Epithelial Cells
GTP-Binding Protein beta Subunits
GTP-Binding Protein gamma Subunits
Kidney
Male
Protein Multimerization
Rats
Rats, Sprague-Dawley
Reperfusion Injury
Xanthenes